Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage.
J Cereb Blood Flow Metab
; 35(5): 843-50, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25605289
ABSTRACT
The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Transdução de Sinais
/
Isquemia Encefálica
/
Conexinas
/
Receptores Purinérgicos P2X7
/
Antagonistas do Receptor Purinérgico P2X
/
Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Revista:
J Cereb Blood Flow Metab
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Espanha